Pain sensitivity and response to pain inhibiting strategies exhibit large individual differences. The genetic portion of such variability can be studied using inbred mouse strains. The underlying genes can be localized and eventually identified using QTL mapping. In an attempt to explain the genetic factors underlying such variability, we propose to perform QTL mapping of four different analgesics: acetaminophen, epbatidine, U50-488, and WIN-55,212-2. Although these analgesics interact with distinct proteins, there exists a moderate to strong correlation among inbred strain responses to them, suggesting that "master" analgesia genes may be identified affecting all types of analgesia. Once QTLs are detected, we will attempt to learn their identity by a combination of candidate gene and positional cloning strategies. Clinical utility of this work may include the development of DNA tests predicting sensitivity to analgesics, novel therapies, and possibly gene therapy for chronic pain states.